CES2 RNA 表达在神经母细胞瘤中的临床意义。
Clinical implications of CES2 RNA expression in neuroblastoma.
机构信息
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
出版信息
J Pediatr Surg. 2013 Mar;48(3):502-9. doi: 10.1016/j.jpedsurg.2012.10.004.
BACKGROUND/PURPOSE: Human carboxylesterase 2 (CES2) is the key enzyme for metabolic activation of irinotecan (CPT-11). The aim was to evaluate the clinical implications of CES2 RNA expression in neuroblastoma cells.
METHODS
CES2 RNA expression was determined by real-time reverse transcription-polymerase chain reaction in five neuroblastoma cell lines and 42 clinical samples of untreated neuroblastoma. Sensitivity to CPT-11 was assessed by WST-8 colorimetric assays. Induction of apoptosis was evaluated by flow cytometry after CPT-11 exposure. Protein expression of CES2 was evaluated by Western blotting analysis. CES2 RNA expression in clinical samples was investigated for its associations with the clinicopathological characteristics.
RESULTS
CES2 RNA expression was observed in neuroblastoma cells, and its expression in neuroblastoma cell lines was positively correlated with sensitivity to CPT-11 and apoptosis after CPT-11 exposure in vitro. CES2 RNA expression was correlated with the protein levels of CES2 in vitro. CES2 RNA expression was significantly higher in patients with a characteristic related to advanced disease.
CONCLUSIONS
Our results suggest the potential of clinical application of CPT-11 in neuroblastoma treatment for patients with advanced disease.
背景/目的：人类羧酸酯酶 2（CES2）是伊立替康（CPT-11）代谢激活的关键酶。本研究旨在评估 CES2 在神经母细胞瘤细胞中的 RNA 表达的临床意义。
方法
采用实时逆转录-聚合酶链反应（real-time RT-PCR）法检测 5 种神经母细胞瘤细胞系和 42 例未经治疗的神经母细胞瘤临床样本中的 CES2 RNA 表达。采用 WST-8 比色法评估对 CPT-11 的敏感性。用流式细胞术检测 CPT-11 暴露后细胞凋亡情况。采用 Western blot 分析检测 CES2 蛋白表达。探讨临床样本中 CES2 RNA 表达与临床病理特征的关系。
结果
在神经母细胞瘤细胞中观察到 CES2 RNA 表达，其在神经母细胞瘤细胞系中的表达与体外 CPT-11 敏感性和 CPT-11 暴露后的细胞凋亡呈正相关。CES2 RNA 表达与体外 CES2 蛋白水平相关。在具有晚期疾病特征的患者中，CES2 RNA 表达显著升高。
结论
我们的研究结果提示，CPT-11 在晚期疾病患者的神经母细胞瘤治疗中具有潜在的临床应用价值。
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